Abstract Introduction Obstructive sleep apnea (OSA) is highly prevalent in children with Down syndrome with estimated prevalence of 45-79%. Current OSA treatments for children with Down syndrome have limited effectiveness, as positive airway pressure therapy is poorly tolerated and adenotonsillectomy is not curative for most children with Down syndrome. The combination of atomoxetine and oxybutynin (ato-oxy) is a promising treatment for OSA in children with Down syndrome. Studies of ato-oxy (and the related treatment AD109, atomoxetine and aroxybutynin) in adults without Down syndrome have identified insomnia as a common adverse effect of treatment that may lead to discontinuation of treatment. Therefore, we evaluated the impact of ato-oxy on insomnia symptoms in children with Down syndrome and OSA. Methods The pediatric insomnia severity index (PISI) was used to evaluate insomnia symptoms in participants in an ongoing clinical trial of ato-oxy for OSA for children (age 6-17 years) with Down syndrome. Participants received 6 months of ato-oxy treatment (0.5 mg/kg atomoxetine and 5 mg oxybutynin). Paired t-tests were used to compare PISI scores at baseline and after treatment. Results 12 participants had data at both baseline and after 6 months of ato-oxy. Baseline sleep onset problem score was 5 ± 3.7 which improved to 3.3 ± 2.0 following ato-oxy treatment (p=0.04). Baseline sleep maintenance problem score was 6 ± 3.0 and improved to 3.4 ± 1.9 following ato-oxy treatment (p=0.005). Conclusion In contrast to ato-oxy treatment in typically developing adults, OSA treatment with ato-oxy in children with Down syndrome showed improvement in insomnia symptoms. Ato-oxy may be particularly beneficial for children with Down syndrome and comorbid insomnia and OSA, particularly as positive airway pressure therapy is often associated with worsened insomnia. These results also highlight the need for studies in special populations as results in typically developing populations may not be generalizable to special populations. Support (if any) Funding provided by NIH (HL151254 and HD109777) and PCORI (IDD-2024C1-37111). All statements in this report, including its findings and conclusions, are solely those of the authors and do not necessarily represent the views of the Patient-Centered Outcomes Research Institute (PCORI), its Board of Governors or Methodology Committee.

IntroductionSleep disordered breathing (SDB) is known to be a comorbidity associated with congenital heart disease (CHD). This review evaluates the role of sleep disorders as a contributing factor to impairments in cardiovascular health, neurocognitive function, and health-related quality of life in individuals with CHD.MethodsA narrative review was conducted across PubMed, Ovid, and Cochrane Library (1990–2025) searches for studies cross-referencing “congenital heart disease” or “Fontan circulation” with sleep-related terms. Inclusion criteria were studies in CHD populations using objective or self-report sleep assessments; exclusions included non-English, non-original data, or conference abstracts. References of included articles were also screened to identify additional potentially relevant articles. Thirty three of 523 articles screened met inclusion criteria.ResultsSDB is prevalent in both children and adults with CHD, with reported rates ranging from 31 to 63% in adults and up to 57% in children. Both obstructive and central sleep apnea are observed. Comorbid SDB is associated with increased inpatient mortality in infants, poorer quality of life in children and adults, neurocognitive impairments, and increased cardiovascular risk including arrhythmias and paradoxical emboli. Evidence for effective treatment remains limited, though lifestyle, behavioral, and ventilation strategies show potential benefit.DiscussionSDB is common in both children and adults with CHD and has a negative association with behavior, cognition and quality of life for people with CHD.

Abstract Introduction Breath-holding spells are benign paroxysmal events occurring in early childhood, most often triggered by emotional upset or painful stimuli. Continuous positive airway pressure (CPAP) therapy is commonly used in pediatric obstructive sleep apnea (OSA), though initiation may be stressful. To our knowledge, there are no prior reports of breath-holding spells associated with CPAP. Here, we describe what appears to be the first reported case of a cyanotic breath-holding spell occurring immediately after CPAP initiation in a 2-year-old child. Report of case(s) A 2-year-old boy with Cornelia de Lange syndrome and severe OSA (Obstructive apnea- hypopnea index of 65 events/hour) had sustained apnea and cyanosis immediately after CPAP initiation in the sleep lab. A rapid response was called and cardiopulmonary resuscitation was started, but patient quickly spontaneously recovered. The patient was subsequently admitted to the hospital for monitoring. CPAP was reattempted twice in the hospital and patient again had apnea with cyanosis and bradycardia. On the first attempt, recorded oxygen saturation decreased from 100% to 18% on CPAP and heart rate decreased from 143 to 70 beats per minute. On a repeat CPAP attempt after one hour, the patient again had apnea and oxygen saturation decreased to 66% and heart rate decreased from 180 to 51. The CPAP mask was removed and the patient spontaneously recovered both times. Given this CPAP intolerance, the patient was discharged home with oxygen at night for treatment of OSA. Overnight oximetry on 0.2 liter per minute of oxygen via nasal cannula showed an oxygen desaturation index of 11 events /hour and 6.1% of the night with an oxygen saturation below 90%. Conclusion Children with Cornelia de Lange syndrome and severe OSA are at a risk for breath – holding spells. CPAP initiation may trigger breath holding spells and sleep medicine clinicians should be aware of this to avoid unnecessary interventions. There is some evidence that behavioral interventions can lesson breath – holding spells in children with Cornelia de Lange syndrome, but treatments other than CPAP may be necessary in some cases. Support (if any)

Obstructive sleep apnea (OSA) is highly prevalent in children with Down syndrome (DS) and current OSA treatments have limited effectiveness. Positive airway pressure therapy is poorly tolerated and adenotonsillectomy is not curative for most children with DS. In our recent trial, the combination of atomoxetine plus oxybutynin (ato-oxy) reduced OSA severity by 51% in children with DS, with considerable variability in responses to treatment. Here we evaluated the potential utility of OSA endotyping, where physiologic characteristics are extracted from clinical polysomnography, to predict ato-oxy treatment response in children with DS. A randomized, double-blind, crossover pilot trial examined the short-term efficacy of ato-oxy in 15 children aged 6 to 17 years with DS and OSA. Participants received 4 weeks of low dose (0.5 mg/kg atomoxetine and 5 mg oxybutynin) as well as 4 weeks of high dose (1.2 mg/kg atomoxetine and 5 mg oxybutynin) in random order. Endotype characteristics including collapsibility (per Vpassive), muscle compensation, loop gain and arousal threshold were extracted from baseline polysomnography. Primary mixed model analysis evaluated the association between baseline collapsibility and ato-oxy response (% reduction in apnea-hypopnea index [AHI]), adjusting for baseline AHI and dose; secondary analyses examined the remaining endotypic characteristics, and further adjustment for BMI percentile. Twelve participants had available data for analysis. Milder collapsibility was associated with a greater treatment response with a 26% greater reduction in AHI per standard deviation reduction in collapsibility (95% confidence interval: [11, 41] %, p=0.002). Greater muscle compensation was associated with a weaker treatment response (−23% [−44, −3], p=0.028), but the association was partially attenuated with additional adjustment for collapsibility (−12%). Arousal threshold and loop gain were not significant predictors. The association with collapsibility was not attenuated with adjustment for BMI (+34 [19, 48] %). In our early-phase trial, milder airway collapsibility and weaker muscle compensation were predictors of a greater ato-oxy treatment response in children with DS which may help identify individuals with DS and OSA more likely to benefit from muscle stimulation targeted therapies in future trials. Funding provided by NIH (R61/R33HL151254, R21HD109777, and R01HL146697) as well as the Lumind-IDSC foundation.

Obstructive sleep apnea (OSA) is a common sleep disorder associated with serious neurological and cardiovascular complications. Intermittent hypoxia and reoxygenation, a key feature of OSA, produces molecular signals that activate various inflammatory pathways, notably the inflammasome—a multiprotein complex that promotes the release of pro-inflammatory cytokines including IL-18 and IL-1β. This results in systemic inflammation, which contributes to the development of the neurological and cardiovascular complications seen in OSA. In this review, we will first examine the pathways through which intermittent hypoxia induces inflammasome activation. Then, we will connect the inflammasome to the downstream neurological and cardiovascular effects of OSA. Finally, we will explore potential interactions between the inflammasome and OSA treatments including Continuous Positive Airway Pressure therapy and glucagon like peptide-1 receptor agonists (GLP-1RAs).

Chiari malformation (CM) type I can cause obstructive sleep apnea (OSA) and central sleep apnea (CSA) as a result of brainstem compression affecting control of breathing and airway muscle tone. Surgical decompression may improve both OSA and CSA. We report a child with CSA due to CM type I resolve without surgical decompression. A 5-year-old boy presented to sleep medicine clinic with known CM type 1 witnessed silent pauses in breathing, excessive daytime sleepiness and unusual movements during sleep. Polysomnography demonstrated severe CSA (central apnea hypopnea index [AHI] 29.7), and REM sleep without atonia. The patient was initiated on Bilevel Positive Airway Pressure therapy Spontaneous Timed mode (BPAP-ST) as well as a trial of acetazolamide 250 mg nightly which was subsequently discontinued as patient was adherent to BPAP-ST. He was compliant with BPAP-ST therapy nightly with residual AHI < 5 and greatly improved daytime sleepiness. Brain magnetic resonance imaging showed low lying and elongated cerebellar tonsils with adequate cerebral spinal fluid (CSF) flow. No surgical intervention beyond monitoring was performed due to adequate CSF flow. Five years later, repeat polysomnography after holding BPAP-ST showed complete resolution of CSA and no evidence of REM sleep without atonia. Based on study results, BPAP-ST was discontinued. Six months after discontinuation of BPAP-ST, patient reports doing well without excessive daytime sleepiness or other sleep-related symptoms. CM is a known cause of both CSA and OSA (as well as REM sleep without atonia) in children and adults which can be effectively managed by positive airway pressure therapy or surgical decompression. In adults, resolution of CM type 1 is exceedingly rare. However, children have been reported to have spontaneous resolution of CM type 1. This is believed to occur due to increased posterior fossa volume with growth allowing for ascent of the cerebellar tonsils. Given this, use of positive airway pressure therapy for sleep apnea and watchful waiting rather than surgical decompression may be an appropriate treatment option in selected cases.

Rationale: Obstructive sleep apnea (OSA) is a common condition that is usually treated by continuous positive airway pressure (CPAP) therapy, but poor adherence is common and is associated with worse patient outcomes and experiences. Patient satisfaction is increasingly adopted as a quality indicator by healthcare systems. Objectives: We tested the hypothesis that peer-driven intervention effected through an interactive voice response (IVR) system leads to better patient satisfaction (primary outcome), care coordination, and CPAP adherence than active control. Methods: We performed a 6-month randomized, parallel-group, controlled trial with CPAP-naive patients recruited from four centers and CPAP-adherent patients who were trained to be mentors delivering support through an IVR system. Measurements and Main Results: In 263 patients, intention-to-treat analysis of global satisfaction for sleep-specific services was better in the intervention group (4.57 ± 0.71 Likert scale score; mean ± SD) than in the active-control group (4.10 ± 1.13; P < 0.001). CPAP adherence was greater in the intervention group (4.5 ± 0.2 h/night; 62.0% ± 3.0% of nights >4 h use) versus the active-control group (3.7 ± 0.2 h/night; 51.4% ± 3.0% of nights >4 h use; P = 0.014 and P = 0.023). When compared with the active-control group, the Patient Assessment of Chronic Illness Care rating was moderately increased by an adjusted difference of 0.33 ± 0.12 (P = 0.009), Consumer Assessment of Healthcare Provider and Systems rating was not different (adjusted difference, 0.46 ± 0.26; P = 0.076), and Client Perception of Coordination Questionnaire was mildly better in the intervention group (adjusted difference, 0.15 ± 0.07; P = 0.035). Conclusions: Patient satisfaction with care delivery, CPAP adherence, and care coordination were improved by peer-driven intervention through an IVR system. New payor policies compensating peer support may enable implementation of this approach. Clinical trial registered with www.clinicaltrials.gov (NCT02056002).

Obstructive sleep apnea is one of the most common sleep disorders. Positive airway pressure therapy is considered the gold standard for treating obstructive sleep apnea. Yet, optimal therapy might not be achieved in some cases of severe obstructive sleep apnea, despite using maximum settings. In this case report, we describe the successful combination of positive airway pressure therapy and atomoxetine-oxybutynin in reducing the apnea-hypopnea index from the severe range to the mild to moderate range. This was also associated with significant improvement in several symptoms including excessive daytime sleepiness and drowsiness while driving. Mitton J, Khan ME, Combs D, Parthasarathy S, Mashaqi S. Images: combined positive air way pressure and atomoxetine-oxybutynin for the treatment of severe obstructive sleep apnea. J Clin Sleep Med. 2025;21(4):743–746.

Abstract Introduction While mortality rates have decreased in patients with congenital heart disease (CHD), numerous comorbidities associated with CHD persist, including decreased health-related quality of life (HRQOL), depressed mood, and sleep problems. Insomnia is known to worsen mood and HRQOL in children without CHD, therefore we examined the relationship between insomnia, mood and HRQOL. Methods We recruited 38 individuals with CHD between the ages of 4-25 years and assessed insomnia, health-related quality of life, anxiety, and depression using the Pediatric Insomnia Severity Index (PISI), Pediatric Quality of Life Inventory (PedsQL), Screen for Child Anxiety Related Disorders (SCARED), and Center for Epidemiological Studies Depression Scale for Children (CES-DC). T-tests were used to compare differences in HRQOL, anxiety, and depression in individuals with CHD with and without comorbid insomnia. Logistic regression was used to assess whether the presence of insomnia can predict increased odds of clinically significant anxiety or depression. Results Individuals with CHD and insomnia (PISI score ≥8) demonstrated significantly lower health-related quality of life, more depressive symptoms, and higher total anxiety compared to individuals with CHD without insomnia. Individuals with insomnia had a mean HRQOL score of 63.1 ± 15.6 vs 77.8 ± 18.9 in the group without insomnia (p=0.03). Individuals with insomnia had a mean total depression score on the CES-DC scale of 21.5 ± 14.6 vs 7.3 ± 5.6 for those without insomnia (p=0.009). Clinically significant depression in the insomnia group was 24 times greater (95% confidence interval [95% CI] 2.3-247.4, p=0.008) compared to those without insomnia. The mean total anxiety score for individuals with insomnia was 25.0 ±19.6 compared with 12.4 ± 10.3 in those without insomnia (p=0.03), and the odds of clinically significant anxiety in the insomnia group vs those without insomnia was 4.44 (95% CI 0.9-21.8, p=0.07). Conclusion Insomnia is associated with markedly worse HRQOL, depression and anxiety in individuals with CHD. Further study is needed to evaluate the role of insomnia recognition and treatment in order to improve HRQOL and mood in children and young adults with CHD. Support (if any) No support

Abstract Introduction Obstructive sleep apnea (OSA) is highly prevalent in children with Down syndrome (DS). Current OSA treatments for children with DS have limited effectiveness, as positive airway pressure therapy is poorly tolerated and adenotonsillectomy is not curative in most children with DS. We recently showed that the combination of atomoxetine and oxybutynin (ato-oxy) reduced OSA severity by 51% in a small trial of children with DS. Health-related quality of life (HRQOL) scores improved with ato-oxy, but the improvement was not statistically significant when examined across all trial participants. Therefore we evaluated if HRQOL improvements were greater in participants with more significant improvement in OSA. Methods We compared baseline characteristics and changes in HR-QOL in children with DS age 7-17 years old who had a response (defined as obstructive apnea-hypopnea index [oAHI] improvement of >50% and reduction of oAHI to < 5 events/hour) vs. those who did not respond to ato-oxy. Participants received 4 weeks of ato-oxy (0.5 mg/kg atomoxetine and 5 mg oxybutynin) with polysomnography and assessment of HR-QOL using the PedsQL along with behavioral assessment using the Conners at baseline and after 4 weeks of treatment. Paired t-tests or chi square tests were used to compare baseline participant characteristics and linear regression with adjustment for baseline was used to compare treatment outcomes. Results 12 participants had data at both baseline and on ato-oxy. 42% of participants had a significant response to ato-oxy. There were no significant differences at baseline between treatment responders and non-responders in demographics, body mass index or OSA severity. Quality of life was significantly higher in ato-oxy responders compared to non-responders. Adjusted mean total PedsQL score was 75 (95% confidence interval: 64, 87) in responders compared to 61 (51, 70) in non-responders, p=0.048. Responders had better scores across Conners domains including attention and behavior, but these were not statistically significant compared to non-responders. Conclusion No characteristics predicted ato-oxy response for OSA treatment in children with DS. Children who had a significant response to ato-oxy had significant improvement in their quality of life. Support (if any) Funding provided by NIH (HL151254 and HD109777) as well as the Lumind-IDSC foundation.

Parthasarathy S, Mashaqi S, Combs D. Naps and cardiovascular disease: you snooze, you lose! J Clin Sleep Med. 2024;20(8); 1225–1226.

Abstract Introduction Children with Down syndrome (DS) are at very high risk for obstructive sleep apnea (OSA), with a prevalence of OSA of 50-79%. Current OSA treatments for children with DS have limited effectiveness, as positive airway pressure therapy is poorly tolerated and adenotonsillectomy is not curative in most children with DS. The combination of atomoxetine and oxybutynin (ato-oxy) is a promising OSA treatment in adults. Ato-oxy has been shown to improve upper airway hypotonia, a key feature of OSA in children with DS, thus it may be particularly effective for OSA in children with DS. Methods We performed a randomized, double-blind, crossover pilot trial examining the short-term efficacy of ato-oxy in 15 children aged 6 to 17 years with DS and OSA. Participants received 4 weeks of low dose (0.5 mg/kg atomoxetine and 5 mg oxybutynin) as well as 4 weeks of high dose (1.2 mg/kg atomoxetine and 5 mg oxybutynin) in random order. Participants underwent polysomnography as well as parent-reported health-related quality of life assessment using the OSA-18 at baseline and at the end of each dosing period. The primary study endpoint was reduction in obstructive apnea-hypopnea index (oAHI) from baseline. Paired t-tests were used to compare baseline to low and high dose ato-oxy. Results 15 participants qualified for randomization and 11 participants had complete data at all points. Baseline oAHI was 7.4 ± 3.7 (mean ± standard deviation), oAHI with low dose ato-oxy was 3.6 ± 3.3 (p=0.001 vs baseline) and oAHI with high dose ato-oxy was 3.9 ± 2.8 (p=0.003 vs baseline). There were no differences in sleep architecture or sleep efficiency between baseline and either dose of ato-oxy. OSA-18 total score was 51.5 ± 18.5 at baseline; improved to 44.6 ± 17.0 (p=0.09) at the end of 4-weeks of low dose ato-oxy; and improved to 45.5 ± 15.7 (p=0.37) at the end of high-dose ato-oxy therapy. The most common adverse effects were irritability and fatigue, and these were generally mild. Conclusion Ato-oxy is a promising treatment for OSA in children with DS. Support (if any) Funding provided by NIH (HL151254 and HD109777) as well as the Lumind-IDSC foundation.

Children with Down syndrome (DS) are at very high risk for obstructive sleep apnea (OSA). Current OSA treatments have limited effectiveness in this population. We evaluated the effectiveness of atomoxetine and oxybutynin (ato-oxy) to treat OSA in children with Down syndrome. Children ages 6–7 years old with Down syndrome and OSA participated in a double-blind crossover clinical trial evaluating two dose regimens of ato-oxy. Participants received low-dose ato-oxy (0.5 mg/kg atomoxetine and 5 mg oxybutynin) and high-dose ato-oxy (1.2 mg/kg atomoxetine and 5 mg oxybutynin) for 1 month in random order. The primary study outcome was change in obstructive apnea-hypopnea index. Health-related quality of life as measured by the OSA-18 as well as changes in sleep architecture were secondary outcomes. Fifteen participants qualified for randomization and 11 participants had complete data at all points. Baseline obstructive apnea-hypopnea index was 7.4 ± 3.7 (mean ± standard deviation), obstructive apnea-hypopnea index with low-dose ato-oxy was 3.6 ± 3.3 (P = .001 vs baseline), and obstructive apnea-hypopnea index with high-dose ato-oxy was 3.9 ± 2.8 (P = .003 vs baseline). No significant sleep architecture differences were present with ato-oxy. No significant difference in OSA-18 score was present. OSA-18 total score was 51 ± 19 at baseline, 45 ± 17 (P = .09) at the end of 4 weeks of low-dose ato-oxy, and 45 ± 16 (P = .37) at the end of high-dose ato-oxy therapy. The most common adverse effects were irritability and fatigue, and these were generally mild. Ato-oxy is a promising treatment for OSA in children with Down syndrome. Clinical Trial Registration: Registry: Clinicaltrials.gov; Name: Medications for Obstructive Sleep Apnea In Children With Down Syndrome (MOSAIC); URL: https://clinicaltrials.gov/ct2/show/NCT04115878 ; Identifier: NCT04115878. Combs D, Edgin J, Hsu C-H, et al. The combination of atomoxetine and oxybutynin for the treatment of obstructive sleep apnea in children with Down syndrome. J Clin Sleep Med. 2023;19(12):2065–2073.

Introduction We conducted this systematic review and meta-analysis (SRMA) to evaluate the impact of bariatric surgery on obstructive sleep apnea (OSA) as represented by the following polysomnography (PSG) parameters: apnea-hypopnea index (AHI), oxygen desaturation index (ODI), mean oxygen desaturation (mean SpO 2 ), total sleep time spent with SpO 2 < 90% (T-90), and the nadir of oxygen saturation (L SpO 2 ). Methods A comprehensive search of the literature was conducted in Ovid MEDLINE, Embase, and Scopus databases from inception to March 31, 2023. Only articles written in English were reviewed. The analysis of all outcomes was performed using a random-effects model. We included 30 studies (two randomized controlled trials and 28 observational studies) in the final quantitative synthesis with a total of 1,369 patients. Results We concluded that bariatric surgery (regardless of the type) was associated with reduction in AHI [MD 23.2 events/h (95%CI 19.7, 26.8)], ODI [MD 26.8 events/h (95%CI 21.6, 32.1)], mean SpO 2 [MD−1.94% (95%CI −2.5, −1.4)], T-90 [MD 7.5min (95%CI 5.0, 10.0)], and L SpO 2 [MD 9.0% (95%CI −11.8, −6.3)]. Conclusion Our SRMA results are updates to previously published results and continue to support the positive impact of bariatric surgery on OSA and sleep-related hypoxia.

Sleep-disordered breathing (obstructive and central sleep apnea) are common in patients with heart failure with reduced ejection fraction. Herein, we report a 69-year-old patient with a history of severe heart failure and refractory ventricular arrhythmia who was diagnosed with a moderate degree of obstructive and central sleep apnea with Cheyne Stokes breathing. He underwent a successful implantation of left ventricular assist device. Our patient had a complete resolution of both obstructive and central sleep apnea 60 days post-LVAD implantation as confirmed by home sleep apnea test.

Abstract Introduction Children with congenital heart disease who undergo a Fontan procedure are at higher risk of reduced health-related quality of life (HR-QOL) compared to age-matched peers. We have previously shown that current sleep disturbances are associated with decreased HR-QOL, but there is no existing longitudinal data on the relationship between sleep disturbance and HR-QOL in children with Fontan circulation. Methods We analyzed data from the Pediatric Heart Network Single Ventricle Reconstruction follow up study to evaluate associations between parent-reported trouble sleeping with HR-QOL as measured by the child health questionnaire (CHQ, measured at age 6 years) as well as the Pediatric Quality of Life questionnaire (PedsQL, measured at baseline as well as age 4, 5 and 6 years) in children with Fontan circulation. Presence of trouble sleeping was assessed at baseline and quality of life was assessed at baseline (age 3 years old) and annually for 3 years. Analysis was performed using the Wilcoxon sum rank test. Results 227 participants had data at baseline (age 3 years), and 196 participants completed HR-QOL measures at all time points. Parent-reported trouble sleeping was reported “often” or “almost always” in 11% of participants. Baseline trouble sleeping predicted decreased HR-QOL at all future time points, particularly psychosocial HR-QOL. Psychosocial HR-QOL as measured by the Peds QL was significantly lower at all time points in the group with trouble sleeping. At age 6 years, psychosocial HR-QOL remained significantly lower in the group with trouble sleeping at baseline on both the PedsQL (median score 78 [interquartile range 63, 90] vs 65 [58, 83], p=0.03) and the CHQ (median t-score 54 [47, 59] vs 47 [42, 53], p=0.002). Conclusion Trouble sleeping in children with Fontan circulation predicts future decreased HR-QOL. Better understanding of sleep problems is needed in children with Fontan circulation as sleep disorder treatment may lead to improved HR-QOL in this at-risk population. Support (If Any) Funding to DC from the American Heart Association and NIH-NHLBI. Single Ventricle Reconstruction study data obtained from the Pediatric Heart Network.

Introduction: Variability and prolongation of ventricular repolarization -measured by changes in QT interval and QT variability are independently associated with ventricular arrhythmias, sudden death, and mortality but such studies did not examine the role of sleep-disordered breathing. We aimed to determine whether sleep-disordered breathing moderated the association between measures of ventricular repolarization and overall mortality. Methods: Eight hundred participants were randomly selected from each of the following four groups in the Sleep Heart Health Study: mild, moderate, severe or no sleep disordered breathing (n = 200 each). Overnight electrocardiograms were analyzed for QTc duration and QT variability (standard deviation of QT intervals, normalized QT interval variance and the short-term interval beat-to-beat QT variability). Cox proportional hazards penalized regression modeling was used to identify predictors of mortality. Results: Eight hundred of 5600 participants were randomly selected. The participants (68 +/- 10 years; 56.8% male) were followed for an average of 8.2 years during which time 222 (28.4%) died. QTc, SDQT, and QTVN were associated with the presence of SDB (p = 0.002, p = 0.014, and p = 0.024, respectively). After adjusting for covariates, the presence of sleep-disordered breathing did not moderate the association between QTc length, QT variability and mortality (p > 0.05). Conclusion: Sleep-disordered breathing was associated with some measures of ventricular repolarization. However, sleep-disordered breathing was not an effect modifier for the relationship between QTc and QT variability and mortality. (C) 2022 Elsevier B.V. All rights reserved.

The novel corona virus that is now known as (SARS-CoV-2) has killed more than six million people worldwide. The disease presentation varies from mild respiratory symptoms to acute respiratory distress syndrome and ultimately death. Several risk factors have been shown to worsen the severity of COVID-19 outcomes (such as age, hypertension, diabetes mellitus, and obesity). Since many of these risk factors are known to be influenced by obstructive sleep apnea, this raises the possibility that OSA might be an independent risk factor for COVID-19 severity. A shift in the gut microbiota has been proposed to contribute to outcomes in both COVID-19 and OSA. To further evaluate the potential triangular interrelationships between these three elements, we conducted a thorough literature review attempting to elucidate these interactions. From this review, it is concluded that OSA may be a risk factor for worse COVID-19 clinical outcomes, and the shifts in gut microbiota associated with both COVID-19 and OSA may mediate processes leading to bacterial translocation via a defective gut barrier which can then foster systemic inflammation. Thus, targeting biomarkers of intestinal tight junction dysfunction in conjunction with restoring gut dysbiosis may provide novel avenues for both risk detection and adjuvant therapy.